recessive autosomal; occurrence is favored by consanguinity; frequency is 0.3/105 with large geographical variations; higher frequenciy observed in Tunisia (10/105, role of consanguinity) and in Japan (1/105); rare in black people

Clinics

Note

xeroderma pigmentosum (XP) is caused by a defect in nucleotide excision repair mechanisms; various clinical aspects and intensity of signs are described according to the gene involved (7 known complement groups) and type of mutation

propensity to various solid tumors (mainly brain tumors, x 10 to 20 fold in comparison with general population )

Treatment

photoprotection; genetic counseling; treatment of malignant tumors

Evolution

progressively increasing number of cutaneous, ocular and other solid tumors; cutaneous atrophy with numerous scars and aesthetic damage; skin abnormalities comparable to what is clinically and histologically observed with aging; blindness; severe mental retardation

Prognosis

2/3 death before adult age

Cytogenetics

Inborn conditions

hypermutability after UV irradiation in cell cultures; no increased of spontaneous chromosome abnormalities in lymphocytes of fribroblastes; however, after UV-exposure an increased number of sister chromatid exchanges (SCE) and chromosome aberrations are observed (mainly chromatid-type abnormalities); fibroblasts express an increased sensitivity to chemical mutagens; there is no cytogenetic feature useful for XP diagnosis

Genes involved and Proteins

Note

the clinical and cytologic XP heterogeneity is the consequence of the genetic heterogeneity: 7 complementation groups (XPA to G) plus an additional variant form, evidenced by somatic cell fusion experiments

the genes involved are: XPA, located in 9q22, XPB, also called ERCC3 (ERCC for Excision-Repair Cross Complementing rodent repair deficiency), located in 2q21, XPC, located in 3p25, XPD, also called ERCC2, located in 19q13, XPE, located on chromosome 11 XPF, also called ERCC4, located in 19q13 XPG, also called ERCC5, located in 13q32, and XPV, also called Pol eta, and located in 6p12-21